The sustained administration of drugs over an extended period of time has significant medical and practical advantages in clinical practice. In recent years, much research has been done in developing systems for the sustained release of biologically active substances, particularly drugs, over periods of time. The purpose of these systems is to dispense the drug or other substance in a controlled manner at a selected physiological site. In the case of drugs used for therapy, presenting the drug in the most efficacious manner to effect treatment is desirable, while simultaneously minimizing complications which may occur as a result of the drug delivery.
Presently available systems for the sustained release of drugs are generally polymeric compositions where the drug or agent is either an integral part of the polymer matrix or layered or contained as a discrete portion of the device. For example, Folkman and Langer in U.S. Pat. No. 4,291,797 describe a delivery device for macromolecules in which the macromolecule is interspersed throughout the polymer matrix.
In U.S. Pat. No. 4,767,628, Hutchinson describes a delivery vehicle formed of polylactide polymer and an acid stable polypeptide interspersed in the matrix.
Higuchi in U.S. Pat. No. 3,625,214 describes a sustained release drug delivery device according to a defined release profile by layering the drug and a bioerodible polymer.
Michaels in U.S. Pat. No. 3,867,519 describes a sustained drug delivery device wherein release of the drug is controlled by the composition of an anionic polyvalent metal cation cross-linked polyelectrolyte.
In U.S. Pat. No. 4,093,709 Choi and Heller describe a controlled release device formed from orthoester and orthocarbonate polymers.
While the above systems are useful, they are not appropriate for some applications, such as delivering water-soluble bioactive factors which react with a local cell population at a physiological site. A need exists for systems that can successfully deliver these agents which have favorable release kinetics and allow soluble agents to interact with local cells.